! oligometastases definition - congressi · pdf fileestanislao arana lumc, leiden, netherlands...

!   OLIGOMETASTASES definition

!   Patient selection

!   Evaluation of therapeutic results

1995

The occasional success of surgical excision of one or a small number of pulmonary mets, brain mets or hepatic mets (e.g., 25% of cure after hepatic resections for metastatic colorectal cancer) lets to hypothesize the theory of oligometastases

• The Halsted theory (T à N à M) proposed that cancer spread is orderly, extending in a contiguous fashion from the primary tumor through the lymphatic to the lymph nodes and then to distant sites (1907). •  A subsequent Hellman theory of systemic disease hypothesis (T à M) proposed that clinically apparent cancer is already a systemic disease (1980). •  A third Hellman & Weichselbaum’ theory of spectrum hypothesis: cancer range between disease that remains localized and disease that is systemic at time of diagnosis à multistep nature of cancer progression (1995).

1995

Hellman & Weichselbaum suggested that for many cancers a few metastases exist at first, before the malignant cells acquire widespread metastatic potential. Consequently, if radical intervention (Surgery or Stereotactic Body Radiotherapy - SBRT) could be delivered during an oligometastatic phase, the intervention could change disease progression in pts who would otherwise have been treated palliatively in most settings (the hierarchy theory)

16:120-130 © 2006

Can a solitary nodule truly be the only metastatic lesion? or is it the first nodule/horseman on the horizon before the horde appears?

16:120-130 © 2006

Can a solitary nodule truly be the metastatic lesion? or is it the first nodule/horseman on the horizon before the horde appears?

16:120-130 © 2006

M1: a solitary metastasis in a single organ M2: oligometastases, designate number and limited to 1 organ (5 nodules, 5 cm in total)

Serum molecular markers as follows: S0: not detectable S1: detectable, low level S2: intermediate level S3: high level

A. no systemic signs: minimal 5% weight loss, minimal lab abnormalities. B. systemic signs: 100% weight loss, cachexia, fevers nexplained, lab abnormalities, (i.e. altered lung function, abnormal liver enzymes)

16:120-130 © 2006

!   Solitary lung mets !   Solitary liver mets !   Solitary brain mets !   Solitary bone mets !   Other solitary site mets:

H&N, eye & orbit, ovary & vagina, heart, intestines

THE MAJOR METASTATIC ORGAN SITES

Definition

An intermediate state of cancer spread between localized disease and wide spread mets

the implication is that oligometastatic disease may be cured with metastasis-directed therapy

2013

OLIGOMETASTASES

Stereotactic Body Radiotherapy

(SBRT)

2013

OLIGOMETASTASES

(SBRT)

•  Incidence has not been well established

•  Prognosis can be derived from surgical reports (lung mets from sarcoma, liver mets from colorectal cancer, oligometastasis from breast cancer)

à this subset of patient can be cured in about 15-20% of cases

•  Diagnosis

à Potential differential genetic signature between samples isolated from pts with few or many mets (e.g., microRNA 200c expression or microRNA signature).

à Hierarchy to the appearance of metastatic sites (i.e., early mets may be of limited nature and early therapy could prevent future spread)

à Potential increase of early identification of oligometastasis with PET-CT (e.g., NSCLC with mets to adrenal gland at diagnosis)

(SBRT) 2013

OLIGOMETASTASES

Incidence has not been well established



•  Diagnosis

à Potential increase of early identification of oligometastasis with PET-CT (e.g., NSCLC with mets to adrenal gland at diagnosis) Hierarchy to the appearance of metastatic sites (i.e., early mets may be of limited nature and early therapy could prevent future spread) Potential differential genetic signature between samples isolated from pts with few or many mets (e.g., microRNA 200c expression or microRNA signature).

(SBRT) 2013

OLIGOMETASTASES

Lung met from sarcoma 19% one met Gadd MA et al: Ann Surg 1993

Incidence of oligometastases

Liver-‐only mets from colorectal cancer 49% one met 38% ≤ 3 mets

Kienski et al: Ann Surg Oncol 2010

Distant failure from breast cancer 16% (median 1,7)

Dorn P et al: Int J Radiat Oncol 2011

Distant failure from lung cancer 19% McManus MP et al: Int J Radiat Oncol Biol Phys 2001

Incidence has not been well established



•  Diagnosis

à Potential increase of early identification of oligometastasis with PET-CT (e.g., NSCLC with mets to adrenal gland at diagnosis) Hierarchy to the appearance of metastatic sites (i.e., early mets may be of limited nature and early therapy could prevent future spread) Potential differential genetic signature between samples isolated from pts with few or many mets (e.g., microRNA 200c expression or microRNA signature).

(SBRT) 2013

OLIGOMETASTASES

SBRT treatment of limited metastases has shown promising local control rates for treated metastases, ranging from 67% to 95% Two- to 3-year survival rates have been reported in the range of 30% to 64% SBRT results compare favorably with surgical results. SBRT is less invasive than surgery and may be more broadly applicable to greater numbers of tumors in various organs

(SBRT) 2013

•  Incidence has not been well established



•  Diagnosis

à Potential increase of early identification of oligometastasis with PET-CT (e.g., NSCLC with mets to adrenal gland at diagnosis)

à  Potential differential genetic signature between phenotype isolated in oligometastatic pts (e.g., microRNA 200c expression or microRNA signature).

(SBRT) 2013

OLIGOMETASTASES

Patient with a limited number of metastases and controlled primary tumor

OLIGO-RECURRENCE

PATIENT SELECTION

3 distinct cohorts of pts with oligometastases !   those who present with oligometastatic disease

!   those with induced oligometastatic disease after cytoreductive therapy

!   those with relapsed oligometastatic disease after curative locoregional therapy

These different groups probably have different prognoses,

so therapeutic approaches might differ

AC Tree, Lancet Oncol 2013;14:e28-37

PATIENT SELECTION

Imaging à Oligometastasis/es

•  Histology

•  Metastatic site

•  KPS

Long latent interval (> 6 months)

Brief latent interval

Radical intent Palliative intent

Surgery SBRT


PATIENT SELECTION


•  Histology

• Metastatic site

• KPS

Long latent interval Brief latent interval


Surgery ? SBRT ?

PATIENT SELECTION

* Please note the ablative radiation effect that is not necessary related to radiosensibility !

Surgery for (?)*

•  kidney clear cell tumor,

•  melanomas, or

•  sarcomas

On the basis of HISTOLOGY à Better survival for breast cancer with respect to colorectal & lung à Radioresponsive vs radioresistant histologies

PATIENT SELECTION


• Histology


• KPS



Surgery ? SBRT ?

PATIENT SELECTION

On the basis of METASTATIC SITE

Surgery •  for peripheral lung mets à

•  for easy accessible liver masses à

•  when spinal stabilization is necessary à

•  to remove bone impingement to the spine à

Radiation therapy

•  in other cases

PATIENT SELECTION


• Histology


•  KPS



Surgery ? SBRT ?

PATIENT SELECTION

On the basis of PERFORMANCE STATUS

Surgery

•  for good PSK pts?

Radiation therapy

•  in the other cases ?!

PATIENT SELECTION


•  Histology


•  KPS



Surgery ? SBRT ?

!   Local control !   Disease-free survival (& Freedom from widespread distant metastasis!) !   Toxicity rate

!   QoL

EVALUATION OF THERAPEUTIC RESULTS

!   Local control rate: 67-95% Note that: most in-field recurrence occur (!) à  2-year in-field control rate (i.e., duration of response) ∼ 20% !   Disease-free survival (& Freedom from widespread distant metastasis?) !   Toxicity rate

!   QoL


The breast cancer patients had a 2-, 4-, and 6-year lesion LC rate of 87%; the nonbreast cancer patients had a 2-, 4-, and 6-year lesion LC rate of 74%, 68%, and 65%, respectively.

LOCAL CONTROL (LC)

breast

nonbreast

!   CT and MRI are routinely used to evaluate response to therapy, with RECIST criteria. !   Postsurgical and postradiotherapy fibrosis and necrosis of both malignant tissue as well as surrounding normal tissue, often making it difficult to differentiate between malignant and non-malignant tissues in surveillance CT and MRI imaging


!   QoL


After SBRT ~ 20% pts had a 2- 4 yrs disease-free survival

~ 20% of DFS

!   Local control !   Disease-free survival (& Freedom from widespread distant metastasis !) !   Toxicity rate

!   QoL


Freedom from widespread distant metastasis survival Widespread distant metastases are defined as distant progression not amenable to resection or locally ablative therapy (i.e., SBRT, stereotactic radiosurgery, radiofrequency ablation, embolization).


!   Local control !   Disease-free survival (& Freedom from widespread distant metastasis!) !   Toxicity rate à Toxicity is directly correlated to: v  administered dose, v  tumor volume, v  tumor site.

!   QoL


tumor site

!   Local control !   Disease-free survival (& Freedom from widespread distant metastasis!) !   Toxicity rate à Toxicity is low if radiation dose constraints to normal tissues are respected

!   QoL



!   QoL


QoL


Since SBRT is associated with low toxicity rates with respect to surgery, the QoL benefit is probably greater

(Tree AC et al Lancet Oncol 2013)

ASTRO 2010

ASTRO 2010

4 N/A

Patients suggestions for questions to add: v  Do you have family support? v  Do you worry about your ability to drive in the future? v  Were you able to understand your procedures, treatments, & medications?

Health care provider suggestions for questions to add: v  Have you experienced weakened relationships with family or friends? v  Do you feel like a burden to family/friends? v  Does MSCC have an effect on sexual function? v  Do you have control of your bowel or bladder? v  Are you worried of becoming dependant on others now? v  Are you more concerned about bodily pain or weakness/paralysis in the arms and/or legs?

ASTRO 2010

Canadian-led International Development of a European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Module for Malignant Spinal Cord Compression

~RESEARCH PROTOCOL~

ODETTE CANCER CENTRE, CANADA Gunita MITERA

Andrew LOBLAW Arjun SAHGAL

CROSS CANCER INSTITUTE, CANADA Brita DANIELSON Alysa FAIRCHID

Fundación Instituto Valenciano de Oncología, Spain Estanislao ARANA

LUMC, LEIDEN, NETHERLANDS Yvette van der LINDEN

TATA MEDICAL CENTER, KOLKATA, INDIA Indranil MALLICK

TATA MEMORIAL CENTRE, MUMBAI, INDIA Ashwini Budrukkar

AUSTRALIA & NEW ZEALAND To be determined at April meeting

GERMANY Dirk RADES

ITALY Ernesto MARANZANO

CONCLUSIONS

Standard RT vs SBRT

Active monitoring vs Surgery

Ultimately, a randomized trial of ablative radiotherapy and/or surgery compared with the standard of care may be necessary to

define the role of ablative modalities in oligometastases.

Giotto - Scrovegni - Christ among the Doctors

PATIENT

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